Like the Ebola epidemic sweeps across West Africa, scientists lack the key genetic data to answer a question that has caused much speculation concerned: is it that the virus becomes more transmissible or more fatal or changes that let him escape diagnostic tests or vaccines acquire? Thousands of blood samples from Ebola patients were sitting in refrigerators in Africa and Europe, intact. And as Science to press, the few groups that new sequence data are not made public.
Researchers are eager for a peek close up on how the virus may be changing. In addition to answering questions about its virulence, genomic data could reveal details about the epidemic, including hot spots of transmission and how often the virus has escaped from its animal reservoir to humans, said Andrew Rambaut, an evolutionary biologist who studies infectious diseases at the University of Edinburgh in the UK. "If this can be done in a timely manner, you can really get a taste of what's going on." But faced with the response of the public health of all consumers in the epidemic, bureaucratic obstacles, and keeping the chaotic records, scientists have had to wait.
proteins that allow the Ebola virus to spread and cause disease are encoded by seven genes sheathed proteins. Mutations in the glycoprotein might affect the efficacy of antibody-based treatments. Other genes, such as those of the polymerase and the VP30 transcription factor, can affect the speed the virus replicates
FIGURE :. VIRALZONE / SIB INSTITUTE SWISS BIOINFORMATICS
in August, the world has its closest molecular appearance of the virus so far, when the researchers released 99 genomes of viruses from 78 patients who were infected in or around Kenema, Sierra Leone, from late May to mid-June. This analysis, published online August 28 in Science , comprised more than half of the known cases in Sierra Leone at the time.
The sequence data, the researchers deposited in public databases as soon as they were generated, showed how the virus changed as it passed from person to person in early epidemic in Sierra Leone, with a variant of disappearing as another gained prominence among the cases later. Since then, the epidemic has exploded into an epidemic, he made more than 13,000 ill and killed but the 5000 team, led by Stephen Pardis Sabeti and Gire at the Broad Institute in Cambridge, Massachusetts, has been unable to import new samples of Sierra Leone. Other groups have been thwarted like.
Several researchers say that to obtain approval of the export of health ministries in difficulty was difficult. "I can only assume that the system is so overwhelmed that treatment samples beyond the simple diagnostic tests are not a high priority," said Rambaut, who was a co-author on the paper sequence in August
Stephan Günther, a virologist at the Bernhard Nocht Institute for Tropical Medicine (BNI) in Hamburg, Germany, and coordinator of the European consortium mobile Laboratory (EMLab), said they were unable to export samples from Nigeria or Liberia. But BNI received samples EMLab mission in Guinea since March and now has close to 3000, he said. (BNI is to store them in its high security laboratory on behalf of the Guinean government, which holds still.)
Günther and his colleagues are not yet sequenced any of the samples, because the staff of the consortium have been busy supporting diagnostic centers in affected countries. "We are all busy with field work," says Günther. "The staff is a bit of a problem." This should help, he said, with a new € 1.7 million ($ 2.1 million) awarded by the European Union to EMLab to research Ebola.
In France, the Pasteur Institute, where the first samples of Guinea were first identified as Ebola, also known exporters delays samples from West Africa but plans to start sequencing of new viral genomes soon. The laboratory of the institute in Dakar recently received samples of Guinea, said Felix Rey, who coordinates Ebola working group of the Institute in Paris. Dakar laboratory will extract RNA and send to Paris for high-throughput sequencing. "We hope to have the virus sequenced from hundreds of samples in the next month," said Rey.
Sabeti and colleagues should soon get their samples Sierra Leone, which was finally cleared for export and arrived in the US last week, said Robert Garry of Tulane University in New Orleans, Louisiana, working with Sabeti. But to accelerate research, she and her colleagues are trying to get funds to send sequencing machines to West Africa. "If we can not get samples here, we'll get sequencers there," she said. The effort will build on the ongoing work of researchers with the African Centre of Excellence for Genomics of Infectious Diseases, a consortium of universities and research institutes in the United States, Nigeria, Sierra Leone and Senegal, which for several years has been training African scientists in the use of genomic tools.
Blood samples are insufficient for genomic studies. Investigators need to know at least where each patient was; Ideally, they will also have clinical information, as if he or she survived. "Only when you have these pieces of information that you can find useful information from the sequences," says Günther and due to keeping spotted files, this information is often lacking. He and his colleagues are working with Doctors Without borders and the World health Organisation to match the samples with relevant information, but the establishment of a database is time and labor, he said.
Meanwhile, the Ebola virus some sequences that were generated from this initial batch of Sierra Leone have not been made public. the US centers for disease control and prevention (CDC) announced in August that he had sequenced the Ebola virus samples in patients treated in the United States. But the data are not placed in deposits of public sequence. It's unfortunate, Rambaut said. "As uS cases of Liberia and we have zero sequences from then until now, even a genome would be interesting and potentially useful, "he said. Duncan MacCannell, a specialist in bioinformatics at the CDC in Atlanta, said Science as the sequences were "shared actively and discussed with the public health community." He said CDC is working to submit sequences to a public database.
new sequences likely will not show the virus is finding new ways to attack or spread, said Rambaut. Instead, the price is a clearer picture of the epidemic. A group of closely related viruses may point to a transmission access point, he said, while unexpectedly various sequences suggest that many cases were detected in progress. Sequence data could also help researchers to tell if there was more than one animal to human introduction.
earlier sequence data have suggested that the virus was undergoing rapid change, but it is not necessarily a sign that it is becoming more dangerous, said Rambaut. "Most RNA viruses mutate rapidly, but the adaptation and functional change is a much slower process." Measles mute almost as quickly as the Ebola virus, but it never evolved to escape the immunity of those already infected or vaccinated for life. Even in a home that great, Rambaut said, "I see no reason to suspect that the virus will change radically its life cycle or its mode of transmission"
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